Mycobacterium leprae is an obligate human parasite which can not be cultured in vitro. The lack of suitable experimental models with which to study the immunological parameters of the human response to this important pathogen has greatly limited leprosy research. Several atypical mycobacterial infections result in a persisting non-fatal systemic disease which bears a number of similarities to human leprosy. Such infections are associated with a profound and continuing state of skin test anergy to both cytoplasmic protein (CPA) and whole cell antigens (WCA) prepared from the infecting organism. Such unresponsiveness is associated with the development of a population of suppressor T-cells within the spleens of the heavily infected mice which are able to ablate the blastogenic responsiveness of indicator T-cells exposed to PHA, CPA or WCA in vitro. High and low responder mice will be exposed to M. avium-intracellulare infections and assayed for delayed hypersensitivity and cell-mediated immunity responses with the passage of time. Development of specific anergy and suppressed cellular responses to the infecting population in vivo will be correlated with the development of suppressor cell activity within the splenic T-cell populations tested in vitro. The effect of several chemotherapeutic and immunotherapeutic regimens will be tested for their ability to restore cellular reactivity to mice heavily infected with M. avium using specific sensitins and specific and nonspecific challenges to determine the presence of an effective cell-mediated immunity. The relevance of the M. avium-infected mouse as an immunological model of human leprosy will be evaluated.